Brain Science Institute, Korea Institute of Science and Technology (KIST), 39-1 Hawolgokdong, Seongbukgu, Seoul 02792 Korea.
Brain Science Institute, Korea Institute of Science and Technology (KIST), 39-1 Hawolgokdong, Seongbukgu, Seoul 02792 Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Korea.
Cell Rep. 2022 Mar 1;38(9):110439. doi: 10.1016/j.celrep.2022.110439.
The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in individuals with Parkinson's disease. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, the input circuit and cellular profile in the STN remain largely unclear. Using neuroanatomical techniques, we construct a comprehensive connectivity map of the indirect and hyperdirect pathways in the mouse STN. Our circuit- and cellular-level connectivities reveal a topographically graded organization with three types of indirect and hyperdirect pathways (external globus pallidus only, STN only, and collateral). We confirm consistent pathways into the human STN by 7 T MRI-based tractography. We identify two functional types of topographically distinct glutamatergic STN neurons (parvalbumin [PV+/-]) with synaptic connectivity from indirect and hyperdirect pathways. Glutamatergic PV+ STN neurons contribute to burst firing. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.
底丘脑核（STN）控制着精神运动活动，是帕金森病患者进行高效深部脑刺激治疗的有效靶点。尽管有证据表明其具有位置依赖性的治疗效果和 STN 内的不同功能，但 STN 中的输入回路和细胞特征在很大程度上仍不清楚。我们使用神经解剖技术构建了小鼠 STN 中的间接和直接通路的综合连接图谱。我们的回路和细胞水平的连接性揭示了具有三种间接和直接通路（仅外苍白球、仅 STN 和侧支）的拓扑分级组织。我们通过基于 7T MRI 的束追踪技术确认了一致的进入人类 STN 的通路。我们确定了两种具有拓扑上不同谷氨酸能 STN 神经元（PV+/-）的功能类型，它们具有来自间接和直接通路的突触连接。谷氨酸能 PV+ STN 神经元有助于爆发式放电。这些数据表明，在协调运动控制和治疗效果的基础上，基底神经节内存在着复杂的信息整合相互作用。
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